7. Project Summary/Abstract This is an application for a K01 Award for Dr. Pushkarskaya, a clinical neuroeconomist at the Yale School of Medicine. Her research focuses on the neurobiology of decision-making under uncertainty in clinical populations, which has implications for diagnostics and treatment development. This line of research is interdisciplinary in nature, requiring expertise in economics, psychology, cognitive and systems neuroscience, neuroimaging, and clinical sciences. Dr. Pushkarskaya already has a strong background in behavioral economics. To gain additional necessary expertise she has assembled a strong and diverse mentoring team. Her primary mentor, Dr. Godfrey Pearlson (NIMH Merit Awardee), is a leading scholar in the neurobiology of major psychiatric disorders. Her co-mentors, Drs. Ifat Levy (neuroeconomics), Christopher Pittenger (neurobiology of obsessive compulsive disorder; OCD), and Douglas Rothman (neuroimaging methods), are world-renowned scholars in their fields. Her collaborators, Drs. David Tolin (psychology of OCD) and Daeyeol Lee (neurobiology and systems neuroscience) are both well-known scholars in relevant disciplines. This K01 will (1) provide required training in (i) the biological bases of behavior, (ii) cognitive and systems neuroscience, and (iii) clinical sciences; and (2) increase Dr. Pushkarskaya's versatility as a clinical neuroeconomist by introducing her to (i) advanced neuroimaging methods (including functional and structural MRI data collection and analysis techniques) and (ii) psychodiagnostic assessment. Training in these new fields of study and methodologies is essential to Dr. Pushkarskaya's success as a clinical neuroeconomist. Profound uncertainty avoidance is a well-recognized characteristic of OCD. Behavioral economics quantifies uncertainty attitudes using three distinct parameters that vary across subjects, are uncorrelated, and predict activation patterns in distinct neurobiological networks in healthy subjects. These parameters are: (i) Risk attitude, which reflects a trade-off between the probability of gains or losses and the magnitude of those gains or losses, (ii) Ambiguity attitude, which reflects the subject's sensitivity to an unknown probability of an uncertain payoff; and (iii) Conflict attitude, which reflects the subject's sensitivity to conflicting information about a probability of an uncertain payoff. To understand the neurobiology of uncertainty intolerance in OCD, it is imperative to study these parameters in OCD concurrently. The proposed study will compare risk (Specific Aim 1), ambiguity (Specific Aim 2), and conflict (Specific Aim 3) attitudes between healthy subjects and OCD patients; will contrast functional and structural correlates of uncertainty attitudes in these groups; and will correlate revealed neuro-behavioral profiles with OCD severity and OCD symptom dimensions. A comprehensive understanding of neurocognitive abnormalities in uncertainty attitudes in OCD and/or OCD symptom dimensions would represent a major conceptual step forward in the analysis of a core aspect of the phenomenology of this disease and may have implications for diagnosis, prognosis, and treatment selection.